ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5430T>G (p.Asp1810Glu) (rs149828124)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168091 SCV000218747 uncertain significance Familial adenomatous polyposis 1 2018-02-02 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 1810 of the APC protein (p.Asp1810Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (rs149828124, ExAC 0.01%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 188182). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000766666 SCV000293248 uncertain significance not provided 2016-05-09 criteria provided, single submitter clinical testing This variant is denoted APC c.5430T>G at the cDNA level, p.Asp1810Glu (D1810E) at the protein level, and results in the change of an Aspartic Acid to a Glutamic Acid (GAT>GAG). This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. APC Asp1810Glu was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Aspartic Acid and Glutamic Acid share similar properties, this is considered a conservative amino acid substitution. APC Asp1810Glu occurs at a position that is conserved across species and is located in a 20-aa beta-catenin down-regulating domain and in the SAMP repeats/axin binding domain (Azzopardi 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether APC Asp1810Glu is pathogenic or benign.
Ambry Genetics RCV000571060 SCV000667409 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000168091 SCV000785047 uncertain significance Familial adenomatous polyposis 1 2017-03-21 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000235919 SCV000691757 likely benign not specified no assertion criteria provided clinical testing

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